DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Withdrawn Objections/Rejections
The previous rejections of claims 11-13 and 17-20 under 35 U.S.C. § 103 are withdrawn in view of the claim amendments.
Claim Status
Applicants' amendments and arguments filed on 06/23/2026 have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the
complete set presently being applied to the instant application.
Claims 14-16 are cancelled.
Claims 1-10 are withdrawn.
Claims 11-13 and 17-20 are under current examination.
Claim Objections
Claim 11 is objected to because of the following informalities: it is suggested that the Markush language “the plasticizer is at least one of a glycerol, glycerol diacetate, and/or glycerol tributyrate” should read “the plasticizer is at least one of a glycerol, glycerol diacetate, or glycerol tributyrate” (see MPEP 2117 I.).
Appropriate correction is required.
Claim Interpretation
The limitation “glass transition (Tg) active pharmaceutical agent (API)” of independent claim 11 and dependent claims 13 and 18 is interpreted as an active pharmaceutical agent that exhibits a glass transition.
New Rejections Necessitated by Claim Amendments
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 11-13 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lulla et al. (US 2010/0285115 A1, published November 11, 2010), hereafter “Lulla”, as evidenced by Agrawal et al. (“Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale” AAPS PharmSciTech 2016, 17, 133-147; of record), hereafter “Agrawal”, and as evidenced by NIH (“Glycerol” https://pubchem.ncbi.nlm.nih.gov/compound/Glycerol).
Regarding instant claim 11, Lulla teaches pharmaceutical compositions containing a combination of atazanavir and ritonavir and methods of making (see entire document, particularly abstract). As noted in the instant specification, atazanavir is an example of a high Tg compound and ritonavir is an example of a lower Tg compound (pg. 2, lines 21-24), and thus both are consistent with the “glass transition (Tg) active pharmaceutical agent (API)” recited in the claim. Lulla teaches that the invention may be manufactured by melt extrusion (paragraph [0059]), where a homogenous melt of one or more drugs, a polymer, and one or more excipients are melted into a liquid or rubbery state and extruded into a solid dispersion (paragraphs [0062]-[0067]). Particularly, Lulla teaches that ritonavir has poor oral bioavailability and can be produced by a hot melt extrusion process to convert the ritonavir into amorphous form, which improves its formulation problems (paragraph [0047]). Further, as evidenced by Agrawal, hot melt extrusion allows conversion of APIs to an amorphous form or dispersion (pg. 133, column 2). As the hot melt extrusion to convert the drug into amorphous form improves the bioavailability of the drug, the method of formulating the compositions of Lulla is interpreted as a method of improving release of the drug. Further, as evidenced by Agrawal, amorphous solid dispersions enhance the bioavailability and solubility of poorly soluble drugs and provides for enhanced dissolution, thus improved release (see “Introduction” at pg. 133-134; pg. 140).
Lulla teaches that both ritonavir and atazanavir can be prepared by extrusion of a substantially homogenous melt of ritonavir or atazanavir and one or more excipients; the ritonavir and atazanavir can be mixed with a water soluble polymer and/or a water insoluble polymer (claims 13-16). Lulla further teaches that plasticizers can be incorporated; plasticizers allow the reduction of process temperatures, decrease the glass transition temperature of the polymer, and reduce the viscosity of the polymer melt (see paragraphs [0070] and [0080]). Examples of plasticizers include glycerin (paragraph [0080]); as evidenced by NIH, glycerin is a synonym for glycerol (pg. 1, “Synonyms”). Lulla teaches a drug to polymer ratio of 1:1 (paragraphs [0077]-[0079]), and that the plasticizer is preferably present in an amount ranging from 0% to 10% to the weight of polymer (paragraph [0080]), and thus 0 to 10% to the weight of the drug. Lulla therefore teaches that the plasticizer can be 10% the weight of the drug, consistent with the 10:1 Tg API: plasticizer ratio of instant claim 11.
Regarding instant claim 12, as noted above, Lulla teaches that the plasticizer content can be up to 10% of the weight of the polymer and the drug, suggesting that it will not be present beyond 10 wt.% of the composition. Lulla further exemplifies in Example 1 at paragraph [0094] a composition with 40 mg of Span 20 plasticizer (see paragraph [0080]) in a total composition of 1110 mg, or 3.6 wt.%, indicating that this amount of plasticizer is suitable for use in the method of Lulla.
Regarding instant claim 13, Lulla exemplifies in Example 1 at paragraph [0094] a composition comprising 100 mg of ritonavir in a total composition of 1110 mg (9.0 wt.%) and in Example 2 at paragraph [0096] a composition comprising 25 mg ritonavir in a total composition of 300 mg (8.3 wt.%). Lulla further teaches that dosages of drugs can be varied for a particular patient depending on factors such as age, weight, general health, severity of condition, etc. (paragraph [0053]), suggesting that one of ordinary skill in the art would be motivated to routinely optimize the amount of active ingredient according to the dosage needs of a particular patient. Per MPEP 2144.05 II. A., “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
Regarding instant claim 17, as noted above, Lulla teaches the inclusion of one or more polymers (see paragraphs [0062]-[0063] and claims 13-16). Water soluble polymers that can be used include co-polymers of polyvinylpyrrolidone (PVP) and vinyl acetate (paragraph [0077]).
Regarding instant claims 18-19, Lulla teaches that atazanavir and ritonavir are protease inhibitors (paragraphs [0032]-[0033]). As noted above, Lulla teaches that both ritonavir and atazanavir can be prepared by extrusion of a substantially homogenous melt of ritonavir or atazanavir and one or more excipients; the ritonavir and atazanavir can be mixed with a water soluble polymer and/or a water insoluble polymer (claims 13-16).
Regarding instant claim 20, Lulla teaches the preferred dosage form of the composition is a solid unit dosage form such as a tablet or capsule (paragraph [0051]-[0052]), and a tablet is the preferred solid dosage form due to its greater stability, smaller bulk, etc. (paragraph [0055]).
Lulla does not teach the claimed active method step of formulating the ASD composition with sufficient specificity to anticipate, but rather renders obvious the instant claims. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to combine the prior art elements taught by Lulla according to known methods to yield predictable results. Here, as described above, Lulla teaches the formulation of atazanavir and ritonavir pharmaceutical compositions by melt extrusion in combination with one or more polymers, and that a hot melt extrusion process can convert ritonavir into amorphous form, which improves its formulation problems, such as poor bioavailability (paragraph [0047]). Further, as evidenced by Agrawal, hot melt extrusion allows conversion of APIs to an amorphous form or dispersion (pg. 133, column 2), and amorphous solid dispersions enhance the bioavailability and solubility of poorly soluble drugs and provides for enhanced dissolution, thus improved release (see “Introduction” at pg. 133-134; pg. 140). Lulla further teaches that inclusion of a plasticizer such as glycerin can allow the reduction of process temperatures and reduce the viscosity of the polymer melt.
Formulating the atazanavir and ritonavir compositions via melt extrusion with a polymer and plasticizer as suggested by Lulla would predictably result in a pharmaceutical composition with reduced process temperatures and improved bioavailability and dissolution, and thus an improved release of a Tg API from an amorphous solid dispersion. Per MPEP 2141 I., "[I]n Sakraida v. AG Pro, Inc., the Court derived . . . the conclusion that when a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417, 82 USPQ2d at 1395-96 (Internal quotations omitted.)”.
Response to Arguments
Applicants’ arguments filed 06/23/2026 have been fully considered.
Regarding the claim rejections under 35 USC § 103, Applicants argue that that the amended claim limitation of a plasticizer being at least one of a glycerol, glycerol diacetate, and/or glycerol tributyrate is not taught by the cited prior art of Smith nor its combination with Rothers and Siriwannakij.
In response, the Examiner notes that, as set forth above, the previous claim rejections under 35 USC § 103 have been withdrawn and new rejections which address the amended claim limitations have been applied. Applicant’s arguments with respect to the teachings of Smith, Rothers, and Siriwannakij are considered moot as the new grounds of rejection do not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached at (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611
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